9-35105734-C-T

Variant names:

• chr9-35105734-C-T
• rs796729631
• NM_025182.4:c.1411G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025182.4(ATOSB):​c.1411G>A​(p.Glu471Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATOSB NM_025182.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.30

Genes affected

ATOSB (HGNC:25666): (atos homolog B) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15788874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATOSB	NM_025182.4	c.1411G>A	p.Glu471Lys	missense_variant	Exon 8 of 9	ENST00000322813.10	NP_079458.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATOSB	ENST00000322813.10	c.1411G>A	p.Glu471Lys	missense_variant	Exon 8 of 9	1	NM_025182.4	ENSP00000319897.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1411G>A (p.E471K) alteration is located in exon 8 (coding exon 6) of the FAM214B gene. This alteration results from a G to A substitution at nucleotide position 1411, causing the glutamic acid (E) at amino acid position 471 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	.;T;T;T;T;T;T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T;.;.;.;.;.;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.16	T;T;T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.1	.;L;L;L;L;L;L
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.2	N;.;.;N;.;N;N
REVEL	Benign	0.10
Sift	Benign	0.049	D;.;.;D;.;D;D
Sift4G	Benign	0.14	T;T;T;T;T;T;T
Polyphen		0.48	.;P;P;P;P;P;P
Vest4		0.20
MutPred		0.45		.;Gain of ubiquitination at E471 (P = 0.0077);Gain of ubiquitination at E471 (P = 0.0077);Gain of ubiquitination at E471 (P = 0.0077);Gain of ubiquitination at E471 (P = 0.0077);Gain of ubiquitination at E471 (P = 0.0077);Gain of ubiquitination at E471 (P = 0.0077);
MVP		0.23
MPC		0.27
ClinPred		0.77	D
GERP RS		4.5
Varity_R		0.24
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs796729631; hg19: chr9-35105731;